TY - JOUR
T1 - Role of Rho family GTPases in CCR1- and CCR5-induced actin reorganization in macrophages
AU - Di Marzio, Paola
AU - Dai, Wei Wei
AU - Franchin, Giovanni
AU - Chan, Amanda Y.
AU - Symons, Marc
AU - Sherry, Barbara
PY - 2005/6/17
Y1 - 2005/6/17
N2 - The β-chemokines, MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5, play a critical role in the selective accumulation and activation of macrophages in inflamed tissues. Herein, we demonstrate that the binding of each of these β-chemokines to their cognate receptors, CCR1 and CCR5, in either macrophages or in CCR1- or CCR5-transfected CHO cells, induced actin reorganization and the formation of lamellipodia that are characteristic of the activation of the Rho family GTPase, Rac. A dominant negative mutant of Rac, but not dominant negative mutants of RhoA or Cdc42, blocked MIP-1α-induced lamellipodia formation. Moreover, this MIP-1α-induced Rac activation and consequent lamellipodia formation is Gi-and phosphoinositide-3 kinase (PI3K)-mediated. Thus, Rac activation is critical for both CCR1- and CCR5-triggered signaling cascades mediating β-chemokine-induced reorganization of the actin cytoskeleton, a process essential for effective recruitment and activation of macrophages in inflammation.
AB - The β-chemokines, MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5, play a critical role in the selective accumulation and activation of macrophages in inflamed tissues. Herein, we demonstrate that the binding of each of these β-chemokines to their cognate receptors, CCR1 and CCR5, in either macrophages or in CCR1- or CCR5-transfected CHO cells, induced actin reorganization and the formation of lamellipodia that are characteristic of the activation of the Rho family GTPase, Rac. A dominant negative mutant of Rac, but not dominant negative mutants of RhoA or Cdc42, blocked MIP-1α-induced lamellipodia formation. Moreover, this MIP-1α-induced Rac activation and consequent lamellipodia formation is Gi-and phosphoinositide-3 kinase (PI3K)-mediated. Thus, Rac activation is critical for both CCR1- and CCR5-triggered signaling cascades mediating β-chemokine-induced reorganization of the actin cytoskeleton, a process essential for effective recruitment and activation of macrophages in inflammation.
KW - Chemokine receptor
KW - GTPases
KW - Lamellipodia
KW - β-Chemokines
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UR - http://www.scopus.com/inward/citedby.url?scp=18844406226&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.04.015
DO - 10.1016/j.bbrc.2005.04.015
M3 - Article
C2 - 15882964
AN - SCOPUS:18844406226
SN - 0006-291X
VL - 331
SP - 909
EP - 916
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -